The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

scholarly journals Combined in silico docking and in vitro antiviral testing for drug repurposing identified lurasidone and elbasvir as SARS-CoV-2 and HCoV-OC43 inhibitors

2020 ◽  
Author(s):  
Mario Milani ◽  
Manuela Donalisio ◽  
Rafaela Milan Bonotto ◽  
Edoardo Schneider ◽  
Irene Arduino ◽  
...  
Keyword(s):  
In Silico ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Large Family ◽  
The Novel ◽  
In Silico Docking ◽  
The Common ◽  
Novel Coronavirus ◽  
Micromolar Range

AbstractThe current emergency of the novel coronavirus SARS-CoV-2 urged the need for broad-spectrum antiviral drugs as the first line of treatment. Coronaviruses are a large family of viruses that already challenged humanity in at least two other previous outbreaks and are likely to be a constant threat for the future. In this work we developed a pipeline based on in silico docking of known drugs on SARS-CoV RNA-dependent RNA polymerase combined with in vitro antiviral assays on both SARS-CoV-2 and the common cold human coronavirus HCoV-OC43. Results showed that certain drugs displayed activity for both viruses at a similar inhibitory concentration, while others were specific. In particular, the antipsychotic drug lurasidone and the antiviral drug elbasvir showed promising activity in the low micromolar range against both viruses with good selective index.

scholarly journals Synthesis, in vitro Antimicrobial Evaluation, Molecular Docking Studies and ADME Prediction of Furan-2-yl-Morpholinophenylpyrimidine Derivatives

2021 ◽  
Vol 33 (5) ◽  
pp. 1090-1098
Author(s):  
M.R. Ezhilarasi ◽  
A.B. Senthieel Khumar ◽  
P. Elavarasan
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
In Silico Docking ◽  
E Coli ◽  
Biological Studies ◽  
Antimicrobial Evaluation ◽  
Microbial Strains ◽  
In Silico Molecular Docking

A new series of novel 4-(furan-2-yl)-6-(4-morpholinophenyl)pyrimidine-amines (4a-c) were synthesized and characterized by elemental analysis and spectral analysis like IR, 1D 1H & 13C NMR. The synthesized compounds 4a-c were evaluated for their biological studies. The zone of inhibitions were examined for synthesized compounds 4a-c besides the identical set of microbial strains, especially that compound 4a against S. aureus, S. pyogenes, E. coli, compound 4b against P. aeruginosa has excellent antibacterial activity. Compound 4c shows good inhibition against C. albicans. Also in silico molecular docking and ADME predictions were carried for all the compounds. The docking studies were examined by two different proteins like 1UAG protein and 1OQA protein. in silico docking provides of the compounds have good docking score compared with the standard. In the ADME predictions all the compounds were met criteria. The synthesized compounds all of them obeyed the drug-likeness properties.

scholarly journals In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Padikkamannil Abishad ◽  
Pollumahanti Niveditha ◽  
Varsha Unni ◽  
Jess Vergis ◽  
Nitin Vasantrao Kurkure ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Antimicrobial Efficacy ◽  
Drug Resistant ◽  
Protein Motifs ◽  
Phytochemical Compounds ◽  
In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

scholarly journals In-vitro Cytotoxicity and in silico Molecular Docking of Alkaloids from Tiliacora acuminata

2020 ◽  
Vol 54 (2s) ◽  
pp. s295-s300
Author(s):  
Jeswiny Rodrigues ◽  
Kirankumar Hullatti ◽  
Sunil Jalalpure ◽  
Pukar Khanal
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
In Vitro Cytotoxicity ◽  
In Silico Molecular Docking

scholarly journals Synthesis, Characterization, in vitro Antimicrobial Evaluation and in silico Molecular Docking and ADME Prediction of 4-Chlorophenyl Furfuran Derivatives bearing Pyrazole Moieties

2020 ◽  
Vol 32 (6) ◽  
pp. 1482-1490
Author(s):  
Manju Mathew ◽  
Raja Chinnamanayakar ◽  
Ezhilarasi Muthuvel Ramanathan
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Adme Prediction ◽  
Antimicrobial Studies ◽  
In Silico Molecular Docking

A series of 1-(5-(5-(4-chlorophenyl)furan-2-yl)-4,5-dihyropyrazol-1-yl ethanone (5a-h) was synthesized through E-(3-(5-(4-chloro-phenyl)furan-2-yl)-1-phenylprop-2-en-1-one (3a-h) with hydrazine monohydrate and sodium acetate. Totally, eight compounds were synthesized and their structures were elucidated by infrared, 1H & 13C NMR, elemental analysis, antimicrobial studies, in silico molecular docking studies and also in silico ADME prediction. Antimicrobial studies of the synthesized compounds showed good to moderate activity against the all the stains compared with standard drugs. in silico Molecular docking study was carried out using bacterial protein and BC protein. Synthesized compounds (5a-h) showed good docking score compared with ciprofloxacin. Antimicrobial study was carried out for 4-chlorophenyl furfuran pyrazole derivatives (5a-h). The results of assessment of toxicities, drug likeness and drug score profiles of compounds (5a-j) are promising

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